Biology subjects

Yahalom, G.

Publications and source records attributed to Yahalom, G..

3 recordsLinked to original sources

bioRxiv2024

Multiparametric quantitative MRI uncovers putamen microstructural changes in Parkinson's Disease

Parkinsons disease (PD) is a progressive neurodegenerative disorder dominated by motor and non-motor dysfunction. Despite extensive research, the in vivo characterization of PD-related microstructural brain changes remains an ongoing challenge, limiting advancements in diagnostic and therapeutic strategies. The putamen, a critical structure within the basal ganglia, plays a key role in regulating movement and is profoundly affected in early PD-related neurodegeneration. In this study, we collected multiparametric quantitative MRI (qMRI) brain data of PD patients and healthy controls, to investigate microstructural alterations in the putamen in PD. We utilized a gradient analysis technique to analyze the spatial variations of various qMRI parameters, including relaxation rates (R1, R2, R2*), water fraction (WF), susceptibility, magnetization transfer saturation (MTsat), and diffusion metrics (MD, FA). Our findings reveal significant spatial gradients and interhemispheric asymmetries in these biophysical properties along the anterior-posterior axis of the putamen. Notably, PD patients exhibited increased water fraction and altered transverse relaxation rate R2*, particularly in the posterior putamen, correlated with motor symptom laterality. These microstructural changes suggest underlying tissue atrophy or neuroinflammatory processes associated with PD. The study underscores the importance of the posterior putamen as a focal point for PD pathology and highlights the potential of localized gradient analysis in detecting subtle yet clinically significant brain changes. The new qMRI dataset provides valuable insights into PD pathology, potentially aiding in the development of more precise diagnostic tools and targeted therapies.

neuroscience↗

bioRxiv2019

Visual self-motion cues are impaired in Parkinson's disease yet over-weighted during visual-vestibular integration

BackgroundParkinsons disease (PD) is prototypically a movement disorder. Although perceptual and motor functions are interdependent, much less is known about perceptual dysfunction in PD. Perceptual deficits can impact activities of daily living, and contribute to motor symptoms, but might go unnoticed if not tested directly. Posture, gait and balance, affected in PD, rely on veridical perception of ones own motion in space. Yet it is unknown whether self-motion perception is impaired in PD. ObjectivesTo test self-motion perception in PD, separately for visual and vestibular cues (unisensory), and multisensory integration thereof. MethodsParticipants (19 early stage PD, 23 age-matched and 20 young adult controls) experienced vestibular (motion platform), visual (optic flow), and combined visual-vestibular self-motion stimuli, and discriminated whether the stimulus headings were rightward or leftward of straight ahead. PD participants and age-matched controls were tested on two visits (PD on and off medication). ResultsPD participants had significantly impaired visual self-motion perception, both on and off medication. This deficit correlated significantly with clinical disease severity. By contrast, their vestibular performance was unimpaired. Remarkably, despite impaired visual self-motion perception, PD participants significantly over-weighted visual cues during multisensory (visual-vestibular) integration. ConclusionsSelf-motion perception is affected already in early stage PD, specifically by impaired visual (vs. vestibular) function, and by suboptimal visual-vestibular integration. This may contribute to impaired balance and gait control. Future investigation into this connection might open up new avenues for alternative therapies to better treat these symptoms. Furthermore, these results may also impact early PD diagnosis and subtyping.

neuroscience↗

bioRxiv2019

Analysis of common and rare VPS13C variants in late onset Parkinson disease

ObjectiveWe aimed to study the role of coding VPS13C variants in a large cohort of late-onset PD (LOPD) patients.\n\nMethodsVPS13C and its untranslated regions were sequenced using targeted next-generation sequencing in 1,567 PD patients and 1,667 controls from 3 cohorts. Association tests of rare potential homozygous and compound heterozygous variants and burden tests for rare heterozygous variants were performed. Common variants were analyzed using logistic regression adjusted for age and sex in each of the cohorts, followed by a meta-analysis.\n\nResultsNo bi-allelic carriers of rare VPS13C variants were found among patients and two carriers of compound heterozygous variants were found in two controls. There was no statistically significant burden of rare (MAF<1%) or very rare (MAF<0.1%) coding VPS13C variants in PD. A VPS13C haplotype including the p.R153H-p.I398I-p.I1132V-p.Q2376Q variants was nominally associated with a reduced risk for PD (meta-analysis of the tagging SNP p.I1132V (OR=0.48, 95%CI=0.28-0.82, p=0.0052). This haplotype was not in linkage disequilibrium (LD) with the known genome-wide association study (GWAS) top hit.\n\nConclusionsOur results do not support a role for rare heterozygous or bi-allelic VPS13C variants in LOPD. Additional genetic replication and functional studies are needed to examine the role of the haplotype identified here associated with reduced risk for PD.

genetics↗